Development of a bioavailability‐based risk assessment approach for nickel in freshwater sediments

To assess nickel (Ni) toxicity and behavior in freshwater sediments, a large‐scale laboratory and field sediment testing program was conducted. The program used an integrative testing strategy to generate scientifically based threshold values for Ni in sediments and to develop integrated equilibrium partitioning‐based bioavailability models for assessing risks of Ni to benthic ecosystems. The sediment testing program was a multi‐institutional collaboration that involved extensive laboratory testing, field validation of laboratory findings, characterization of Ni behavior in natural and laboratory conditions, and examination of solid phase Ni speciation in sediments. The laboratory testing initiative was conducted in 3 phases to satisfy the following objectives: 1) evaluate various methods for spiking sediments with Ni to optimize the relevance of sediment Ni exposures; 2) generate reliable ecotoxicity data by conducting standardized chronic ecotoxicity tests using 9 benthic species in sediments with low and high Ni binding capacity; and, 3) examine sediment bioavailability relationships by conducting chronic ecotoxicity testing in sediments that showed broad ranges of acid volatile sulfides, organic C, and Fe. A subset of 6 Ni‐spiked sediments was deployed in the field to examine benthic colonization and community effects. The sediment testing program yielded a broad, high quality data set that was used to develop a Species Sensitivity Distribution for benthic organisms in various sediment types, a reasonable worst case predicted no‐effect concentration for Ni in sediment (PNECsediment), and predictive models for bioavailability and toxicity of Ni in freshwater sediments. A bioavailability‐based approach was developed using the ecotoxicity data and bioavailability models generated through the research program. The tiered approach can be used to fulfill the outstanding obligations under the European Union (EU) Existing Substances Risk Assessment, EU Registration, Evaluation, Authorisation, and Regulation of Chemicals (REACH), and other global regulatory initiatives. Integr Environ Assess Manag 2016;12:735–746. © 2015 SETACKey PointsA comprehensive, representative sediment toxicity database is available to support risk assessment of Ni in freshwater sediments.Sediment Ni ecotoxicity data were gathered from studies that used spiking approaches that resulted in Ni‐enriched sediments resembling naturally contaminated sediments, thus increasing their relevance.Bioavailability of Ni in sediments, which is controlled by acid volatile sulfides (AVS), varies among different species, with actively bioturbating species showing a lower slope in the relationship between decreasing toxicity with increasing AVS.A bioavailability‐based, tiered approach is presented, where the first tier involves comparison of ambient total Ni concentrations with a RWC threshold value of 136 mg Ni/kg. Site‐specific AVS can be used to calculate a site‐specific threshold if ambient Ni is greater than 136 mg Ni/kg.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134197/1/ieam1720.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134197/2/ieam1720_am.pd

Asymmetric interlimb transfer of concurrent adaptation to opposing dynamic forces

Interlimb transfer of a novel dynamic force has been well documented. It has also been shown that unimanual adaptation to opposing novel environments is possible if they are associated with different workspaces. The main aim of this study was to test if adaptation to opposing velocity dependent viscous forces with one arm could improve the initial performance of the other arm. The study also examined whether this interlimb transfer occurred across an extrinsic, spatial, coordinative system or an intrinsic, joint based, coordinative system. Subjects initially adapted to opposing viscous forces separated by target location. Our measure of performance was the correlation between the speed profiles of each movement within a force condition and an ‘average’ trajectory within null force conditions. Adaptation to the opposing forces was seen during initial acquisition with a significantly improved coefficient in epoch eight compared to epoch one. We then tested interlimb transfer from the dominant to non-dominant arm (D → ND) and vice-versa (ND → D) across either an extrinsic or intrinsic coordinative system. Interlimb transfer was only seen from the dominant to the non-dominant limb across an intrinsic coordinative system. These results support previous studies involving adaptation to a single dynamic force but also indicate that interlimb transfer of multiple opposing states is possible. This suggests that the information available at the level of representation allowing interlimb transfer can be more intricate than a general movement goal or a single perceived directional error

Synaptotagmin 5 regulates Ca2+-dependent Weibel-Palade body exocytosis in human endothelial cells.

Membrane protein insertion is an essential cellular process. The broad biophysical and topological range of membrane proteins necessitates multiple insertion pathways, which remain incompletely defined. Here, we have discovered a new membrane protein insertion pathway, identified the class of substrates it handles, explained why other known pathways do not work for these substrates and reconstituted the pathway using purified components

Formal verification techniques for model transformations: A tridimensional classification

In Model Driven Engineering (Mde), models are first-class citizens, and model transformation is Mde's "heart and soul". Since model transformations are executed for a family of (conforming) models, their validity becomes a crucial issue. This paper proposes to explore the question of the formal verification of model transformation properties through a tridimensional approach: the transformation involved, the properties of interest addressed, and the formal verification techniques used to establish the properties. This work is intended for a double audience. For newcomers, it provides a tutorial introduction to the field of formal verification of model transformations. For readers more familiar with formal methods and model transformations, it proposes a literature review (although not systematic) of the contributions of the field. Overall, this work allows to better understand the evolution, trends and current practice in the domain of model transformation verification. This work opens an interesting research line for building an engineering of model transformation verification guided by the notion of model transformation intent

ATP13A2 deficiency disrupts lysosomal polyamine export

ATP13A2 (PARK9) is a late endolysosomal transporter that is genetically implicated in a spectrum of neurodegenerative disorders, including Kufor-Rakeb syndrome—a parkinsonism with dementia1—and early-onset Parkinson’s disease2. ATP13A2 offers protection against genetic and environmental risk factors of Parkinson’s disease, whereas loss of ATP13A2 compromises lysosomes3. However, the transport function of ATP13A2 in lysosomes remains unclear. Here we establish ATP13A2 as a lysosomal polyamine exporter that shows the highest affinity for spermine among the polyamines examined. Polyamines stimulate the activity of purified ATP13A2, whereas ATP13A2 mutants that are implicated in disease are functionally impaired to a degree that correlates with the disease phenotype. ATP13A2 promotes the cellular uptake of polyamines by endocytosis and transports them into the cytosol, highlighting a role for endolysosomes in the uptake of polyamines into cells. At high concentrations polyamines induce cell toxicity, which is exacerbated by ATP13A2 loss due to lysosomal dysfunction, lysosomal rupture and cathepsin B activation. This phenotype is recapitulated in neurons and nematodes with impaired expression of ATP13A2 or its orthologues. We present defective lysosomal polyamine export as a mechanism for lysosome-dependent cell death that may be implicated in neurodegeneration, and shed light on the molecular identity of the mammalian polyamine transport system

Pycnogenol® and Ginkgo biloba extract: effect on peroxynitrite-oxidized sarcoplasmic reticulum Ca2+-ATPase

The effect of two natural standardized plant extracts, Pycnogenol® and EGb 761, on sarcoplasmic reticulum Ca2+-ATPase (SERCA) activity and posttranslational modifications induced by peroxynitrite was investigated to assess their possible protective role. EGb 761 was found to have a protective effect on SERCA activity in the concentration range of 5–40 µg/ml. On the other hand, Pycnogenol® caused a decrease of SERCA activity at concentrations of 25 µg/ml. EGb 761 did not prevent protein carbonyl formation upon oxidation with peroxynitrite. On the contrary, Pycnogenol® at the concentrations of 5 and 10 µg/ml significantly decreased the level of protein carbonyls by 44% and 54%, respectively. Neither Pycnogenol® nor EGb 761 exerted a protective effect against thiol group oxidation.The plant extracts studied modulated peroxynitrite-injured SERCA activity by different ways and failed to correlate with posttranslational modifications. Their effect seems to be associated with their ability to change SERCA conformation rather than by their antioxidant capacity